Many proteins involved in regulating genome expression, chromosomal replication and cellular proliferation function through their ability to bind specific sites in the genome. Transcriptional activators, for example, bind to specific promoter sequences and recruit chromatin modifying complexes and the transcription apparatus to initiate RNA synthesis. The remodeling of gene expression that occurs as cells move through the cell cycle, or when cells sense changes in their environment, is effected in part by changes in the DNA-binding status of transcriptional activators. Distinct DNA-binding proteins are also associated with centromeres, telomeres, and origins of DNA replication, where they regulate chromosome replication and maintenance. Although considerable knowledge of many fundamental aspects of gene expression and DNA replication has been obtained from studies of DNA-binding proteins, an understanding of these proteins and their functions is limited by our knowledge of their binding sites in the genome.
In addition, regulation of the cell cycle clock is effected through a controlled program of gene expression and oscillations in the activity of the cyclin-dependent (CDK) family of protein kinases. Much is known about the control of stage-specific functions by CDKs and their regulators during the cell cycle (Mendenhall and Hodge, 1998; Morgan, 1997; Nurse, 2000). A more complete understanding of cell cycle regulation is constrained, however, by our limited knowledge of the transcriptional regulatory network that controls the clock. Additional knowledge of cell cycle regulation would make it clearer how the transcriptional and post-transcriptional regulatory networks that control the complex and highly regulated processes are involved in the cell cycle and make it possible to produce a genetic/regulatory network map and to not only identify steps in the pathway, but also connect the cell cycle with other cellular functions.
Proteins which bind to a particular region of DNA can be detected using known methods. However, a need exists for a method which allows examination of the binding of proteins to DNA across the entire genome of an organism.